tbuckley/cabot-search huggingface dataset:
Assessment of Medical Cannabis and Health-Related Quality of Life
Authors: Thomas R. Arkell, Luke A. Downey, Amie C. Hayley, Sebastian Roth
Journal: JAMA Network Open (2023)

Importance The use of cannabis as a medicine is becoming increasingly prevalent. Given the diverse range of conditions being treated with medical cannabis, as well as the vast array of products and dose forms available, clinical evidence incorporating patient-reported outcomes may help determine safety and efficacy. Objective To assess whether patients using medical cannabis report improvements in health-related quality of life over time. Design, Setting, and Participants This retrospective case series study was conducted at a network of specialist medical clinics (Emerald Clinics) located across Australia. Participants were patients who received treatment for any indication at any point between December 2018 and May 2022. Patients were followed up every mean (SD) 44.6 (30.1) days. Data for up to 15 follow-ups were reported. Statistical analysis was conducted from August to September 2022. Exposure Medical cannabis. Product types and cannabinoid content varied over time in accordance with the treating physician’s clinical judgement. Main Outcomes and Measures The main outcome measure was health-related quality of life as assessed using the 36-Item Short Form Health Survey (SF-36) questionnaire. Results In this case series of 3148 patients, 1688 (53.6%) were female; 820 (30.2%) were employed; and the mean (SD) age was 55.9 (18.7) years at baseline before treatment. Chronic noncancer pain was the most common indication for treatment (68.6% [2160 of 3148]), followed by cancer pain (6.0% [190 of 3148]), insomnia (4.8% [152 of 3148]), and anxiety (4.2% [132 of 3148]). After commencing treatment with medical cannabis, patients reported significant improvements relative to baseline on all 8 domains of the SF-36, and these improvements were mostly sustained over time. After controlling for potential confounders in a regression model, treatment with medical cannabis was associated with an improvement of 6.60 (95% CI, 4.57-8.63) points to 18.31 (95% CI, 15.86-20.77) points in SF-36 scores, depending on the domain (all P &amp;amp;lt; .001). Effect sizes (Cohen d ) ranged from 0.21 to 0.72. A total of 2919 adverse events were reported, including 2 that were considered serious. Conclusions and Relevance In this case series study, patients using medical cannabis reported improvements in health-related quality of life, which were mostly sustained over time. Adverse events were rarely serious but common, highlighting the need for caution with prescribing medical cannabis.
Error in Figure 3
Journal: JAMA Network Open (2023)

Ali Rowhani-Rahbar, MD, MPH, PhD; Sabrina Oesterle, PhD; Emma L. Gause, MS, MA; Margaret R. Kuklinski, PhD; Alice M. Ellyson, MS, PhD; Julia P. Schleimer, MPH; Kimberly Dalve, MA; Elizabeth H. Weybright, PhD; John S. Briney, MA, MPA; J. David Hawkins, PhD
CD49d Expression Identifies a Biologically Distinct Subtype of Chronic Lymphocytic Leukemia with Inferior Progression-Free Survival on BTK Inhibitor Therapy
Authors: Anfal Alsadhan, Jonathan Chen, Erika M. Gaglione, Chingiz Underbayev, Pamela L. Tuma, Xin Tian, Lita A. Freeman, Sivasubramanian Baskar, Pia Nierman, Susan Soto, Andy Itsara, Inhye E. Ahn, Clare Sun, Elena Bibikova, Tanja Nicole Hartmann, Maissa Mhibik, Adrian Wiestner
Journal: Clinical Cancer Research (2023)

To determine the role of CD49d for response to Bruton's tyrosine kinase inhibitors (BTKis) in patients with chronic lymphocytic leukemia (CLL).In patients treated with acalabrutinib (n=48), CD49d expression, VLA-4 integrin activation, and tumor transcriptomes of CLL cells were assessed. Clinical responses to BTKis were investigated in acalabrutinib (n=48; NCT02337829), and ibrutinib (n=73; NCT01500733) treated patients.In patients treated with acalabrutinib, treatment induced lymphocytosis was comparable for both subgroups but resolved more rapidly for CD49d+ cases. Acalabrutinib inhibited constitutive VLA-4 activation but was insufficient to block BCR and CXCR4 mediated inside-out activation. Transcriptomes of CD49d+ and CD49d- cases were compared using RNA sequencing at baseline and at 1 and 6 months on treatment. Gene set enrichment analysis revealed increased constitutive NF-кB and JAK-STAT signaling, enhanced survival, adhesion, and migratory capacity in CD49d+ over CD49d- CLL that was maintained during therapy. In the combined cohorts of 121 BTKi treated patients, 48 (39.7%) progressed on treatment with BTK and/or PLCG2 mutations detected in 87% of CLL progressions. Consistent with a recent report, homogeneous and bimodal CD49d positive cases (the latter having concurrent CD49d+ and CD49d- CLL subpopulations, irrespective of the traditional 30% cutoff), had a shorter time to progression of 6.6 years, while 90% of cases homogenously CD49d negative were estimated progression-free at 8 years (P = .0004).CD49d/VLA-4 emerges as a microenvironmental factor that contributes to BTKi resistance in CLL. The prognostic value of CD49d is improved by considering bimodal CD49d expression.
Recombinant production of a diffusible signal factor inhibits <i>Salmonella</i> invasion and animal carriage
Authors: Mudasir Ali Rather, Rimi Chowdhury, Paulina D. Pavinski Bitar, Craig Altier
Journal: Gut Microbes (2023)

The complex chemical environment of the intestine is defined largely by the metabolic products of the resident microbiota. Enteric pathogens, elegantly evolved to thrive in the gut, use these chemical products as signals to recognize specific niches and to promote their survival and virulence. Our previous work has shown that a specific class of quorum-sensing molecules found within the gut, termed diffusible signal factors (DSF), signals the repression of Salmonella tissue invasion, thus defining a means by which this pathogen recognizes its location and modulates virulence to optimize its survival. Here, we determined whether the recombinant production of a DSF could reduce Salmonella virulence in vitro and in vivo. We found that the most potent repressor of Salmonella invasion, cis-2-hexadecenoic acid (c2-HDA), could be recombinantly produced in E. coli by the addition of a single exogenous gene encoding a fatty acid enoyl-CoA dehydratase/thioesterase and that co-culture of the recombinant strain with Salmonella potently inhibited tissue invasion by repressing Salmonella genes required for this essential virulence function. Using the well characterized E. coli Nissle 1917 strain and a chicken infection model, we found that the recombinant DSF-producing strain could be stably maintained in the large intestine. Further, challenge studies demonstrated that this recombinant organism could significantly reduce Salmonella colonization of the cecum, the site of carriage in this animal species. These findings thus describe a plausible means by which Salmonella virulence may be affected in animals by in situ chemical manipulation of functions essential for colonization and virulence.
A commentary on ‘Post-cholecystectomy major bile duct injury: Ideal time to repair based on a multi-center randomized controlled trial with promising results’
Authors: Yan Feng, Qian Zhang, Xingru Wang
Journal: International Journal of Surgery (2023)

Department of Hepatobiliary Surgery, Qujing Second People's Hospital of Yunnan Province, Qujing, China Yan Feng, Qian Zhang, Yan Feng and Qian Zhang contributed equally to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: Department of Hepatobiliary Surgery,Qujing Second People's Hospital of Yunnan, Province, CHINA, Tel: +8615887473369. E-mail address: [email protected] (X. Wang) This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Hybrid allele-specific ChIP-seq analysis identifies variation in brassinosteroid-responsive transcription factor binding linked to traits in maize
Authors: Thomas Hartwig, Michael Banf, Gisele Passaia Prietsch, Jia-Ying Zhu, Isabel Mora-Ramírez, Jos H M Schippers, Samantha J Snodgrass, Arun S Seetharam, Bruno Huettel, Judith M Kolkman, Jinliang Yang, Julia Engelhorn, Zhi-Yong Wang
Journal: Genome biology (2023)

Abstract Background Genetic variation in regulatory sequences that alter transcription factor (TF) binding is a major cause of phenotypic diversity. Brassinosteroid is a growth hormone that has major effects on plant phenotypes. Genetic variation in brassinosteroid-responsive cis-elements likely contributes to trait variation. Pinpointing such regulatory variations and quantitative genomic analysis of the variation in TF-target binding, however, remains challenging. How variation in transcriptional targets of signaling pathways such as the brassinosteroid pathway contributes to phenotypic variation is an important question to be investigated with innovative approaches. Results Here, we use a hybrid allele-specific chromatin binding sequencing (HASCh-seq) approach and identify variations in target binding of the brassinosteroid-responsive TF ZmBZR1 in maize. HASCh-seq in the B73xMo17 F1s identifies thousands of target genes of ZmBZR1. Allele-specific ZmBZR1 binding (ASB) has been observed for 18.3% of target genes and is enriched in promoter and enhancer regions. About a quarter of the ASB sites correlate with sequence variation in BZR1-binding motifs and another quarter correlate with haplotype-specific DNA methylation, suggesting that both genetic and epigenetic variations contribute to the high level of variation in ZmBZR1 occupancy. Comparison with GWAS data shows linkage of hundreds of ASB loci to important yield and disease-related traits. Conclusion Our study provides a robust method for analyzing genome-wide variations of TF occupancy and identifies genetic and epigenetic variations of the brassinosteroid response transcription network in maize.
OTUD1 promotes pathological cardiac remodeling and heart failure by targeting STAT3 in cardiomyocytes
Authors: Mengyang Wang, Xue Han, Tianxiang Yu, Minxiu Wang, Wu Luo, Chunpeng Zou, Xiuyun Li, Gao Li, Gaojun Wu, Yi Wang, Guang Liang
Journal: Theranostics (2023)

Rationale: Understanding the molecular mechanisms of deleterious cardiac remodeling is important for the development of treatments for heart failure.Recent studies have highlighted a role of deubiquitinating enzymes in cardiac pathophysiology.In the present study, we screened for alteration of deubiquitinating enzymes in experimental models of cardiac remodeling, which indicated a potential role of OTU Domain-Containing Protein 1 (OTUD1).Methods: Wide-type or OTUD1 knockout mice with chronic angiotensin II infusion and transverse aortic constriction (TAC) were utilized to develop cardiac remodeling and heart failure.We also overexpressed OTUD1 in mouse heart with AAV9 vector to validate the function of OTUD1.LC-MS/MS analysis combined with Co-IP was used to identify the interacting proteins and substrates of OTUD1.Results: We found that OTUD1 is elevated in mouse heart tissues following chronic angiotensin II administration.OTUD1 knockout mice were significantly protected against angiotensin II-induced cardiac dysfunction, hypertrophy, fibrosis and inflammatory response.Similar results were obtained in the TAC model.Mechanistically, OTUD1 bounds to the SH2 domain of STAT3 and causes deubiquitination of STAT3.Cysteine at position 320 of OTUD1 exerts K63 deubiquitination to promote STAT3 phosphorylation and nuclear translocation, thereby increasing STAT3 activity to induce inflammatory responses, fibrosis, and hypertrophy in cardiomyocytes.Finally, OTUD1 overexpression by AAV9 vector increases Ang II-induced cardiac remodeling in mice and OTUD1-regulated responses can be inhibited by blocking STAT3.Conclusion: Cardiomyocyte OTUD1 promotes pathological cardiac remodeling and dysfunction by deubiquitinating STAT3.These studies have highlighted a novel role of OTUD1 in hypertensive heart failure and identified STAT3 as a target of OTUD1 in mediating these actions.
Clinical practice guideline and expert consensus recommendations for rehabilitation among children with cancer: A systematic review
Authors: Allison J. L’Hotta, Samantha B. Randolph, Ben Reader, Kim Lipsey, Allison A. King
Journal: CA A Cancer Journal for Clinicians (2023)

Increased attention to the rehabilitation needs of children with cancer is vital to enhance health, quality-of-life, and productivity outcomes. Among adults with cancer, rehabilitation recommendations are frequently incorporated into guidelines, but the extent to which recommendations exist for children is unknown. Reports included in this systematic review are guideline or expert consensus reports containing recommendations related to rehabilitation referral, evaluation, and/or intervention for individuals diagnosed with cancer during childhood (younger than 18 years). Eligible reports were published in English from January 2000 to August 2022. Through database searches, 42,982 records were identified; 62 records were identified through citation and website searching. Twenty-eight reports were included in the review: 18 guidelines and 10 expert consensus reports. Rehabilitation recommendations were identified in disease-specific (e.g., acute lymphoblastic leukemia), impairment-specific (e.g., fatigue, neurocognition, pain), adolescent and young adult, and long-term follow-up reports. Example recommendations included physical activity and energy-conservation techniques to address fatigue, referral to physical therapy for chronic pain management, ongoing psychosocial surveillance, and referral to speech-language pathology for those with hearing loss. High-level evidence supported rehabilitation recommendations for long-term follow-up care, fatigue, and psychosocial/mental health screening. Few intervention recommendations were included in guideline and consensus reports. In this developing field, it is critical to include pediatric oncology rehabilitation providers in guideline and consensus development initiatives. This review enhances the availability and clarity of rehabilitation-relevant guidelines that can help prevent and mitigate cancer-related disability among children by supporting access to rehabilitation services.
Population Genomics Provide Insights into the Evolution and Adaptation of the Asia Corn Borer
Authors: Yan Peng, Minghui Jin, Zhimin Li, Hongran Li, Lei Zhang, Songmiao Yu, Zhuting Zhang, Ruyi Fan, Jimin Liu, Qi Xu, Kenneth Wilson, Yutao Xiao
Journal: Molecular Biology and Evolution (2023)

Abstract Understanding the genetic basis of pest adaptive evolution and the risk of adaptation in response to climate change is essential for the development of sustainable agricultural practices. However, the genetic basis of climatic adaptation for the Asian corn borer (ACB), Ostrinia furnacalis, the main pest of corn in Asia and Oceania, is poorly understood. Here, we revealed the genomic loci underlying the climatic adaptation and evolution in ACB by integrating population genomic and environmental factors. We assembled a 471-Mb chromosome-scale reference genome of ACB and resequenced 423 individuals covering 27 representative geographic areas. We inferred that the ACB effective population size changes tracked with the global temperature and followed by a recent decline. Based on an integrated analysis of whole-genome selection scans and genome-wide genotype–environment association studies, we revealed the genetic basis of ACB adaption to diverse climates. For diapause traits, we identified a major effect association locus containing a circadian clock gene (period) by analyzing a diapause-segregating population. Moreover, our predictions indicated that the northern populations were more ecologically resilient to climate change than the southern populations. Together, our results revealed the genomic basis for ACB environmental adaptation and provided potential candidate genes for future evolutionary studies and genetic adaptation to climate change, intending to maintain the efficacy and sustainability of novel control techniques.
Taming Glioblastoma in “Real Time”: Integrating Multimodal Advanced Neuroimaging/AI Tools Towards Creating a Robust and Therapy Agnostic Model for Response Assessment in Neuro-Oncology
Authors: Laiz Laura de Godoy, Sanjeev Chawla, Steven Brem, Suyash Mohan
Journal: Clinical Cancer Research (2023)

The highly aggressive nature of glioblastoma carries a dismal prognosis despite aggressive multimodal therapy. Alternative treatment regimens, such as immunotherapies, are known to intensify the inflammatory response in the treatment field. Follow-up imaging in these scenarios often mimics disease progression on conventional MRI, making accurate evaluation extremely challenging. To this end, revised criteria for assessment of treatment response in high-grade gliomas were successfully proposed by the RANO Working Group to distinguish pseudoprogression from true progression, with intrinsic constraints related to the post-contrast T1-weighted MRI sequence. To address these existing limitations, our group proposes a more objective and quantifiable "treatment agnostic" model, integrating into the RANO criteria advanced multimodal neuroimaging techniques, such as diffusion tensor imaging (DTI), dynamic susceptibility contrast-perfusion weighted imaging (DSC-PWI), dynamic contrast enhanced (DCE)-MRI , MR spectroscopy, and amino acid-based PET imaging tracers, along with artificial intelligence tools (radiomics, radiogenomics, and radiopathomics) and molecular information to address this complex issue of treatment-related changes versus tumor progression in 'real-time', particularly in the early post-treatment window. Our Perspective delineates the potential of incorporating multimodal neuroimaging techniques to improve consistency and automation for the assessment of early treatment response in neuro-oncology.
Effect of hyperthermic intraperitoneal chemotherapy on survival and recurrence rates in advanced gastric cancer: a systematic review and meta-analysis
Authors: Maitreyi Patel, Amandeep Arora, Dipankar Mukherjee, Samrat Mukherjee
Journal: International Journal of Surgery (2023)

Background: Around 5–20% of patients who undergo surgery for advanced gastric cancer (AGC), which invades into the muscularis propria or beyond, have peritoneal carcinomatosis. The peritoneal recurrence rate is 10–54%, which is associated with a poor prognosis. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in AGC with and without peritoneal carcinomatosis is not clearly defined. Methods: The authors conducted a meta-analysis, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, of the clinical trials and high-quality nonrandomized studies evaluating the role of HIPEC in AGC over the last 10 years. The studies were searched in PubMed, EMBASE, MEDLINE, and Cochrane databases between January 2011 to December 2021. Clinical data including overall survival, recurrence free survival, overall recurrence rate, peritoneal recurrence rate, and complications analyzed using RevMan 5.4. Results: Six randomized controlled trials and 10 nonrandomized studies, comprising a total of 1700 patients were included. HIPEC was associated with significantly improved OS at 3 [odd ratio (OR) 1.89, 95% CI: 1.17–3.05] and 5 years (OR 1.87, 95% CI: 1.29–2.71). HIPEC was associated with reduced overall recurrence (OR 0.49, 95% CI: 0.31–0.80) and peritoneal recurrence (OR 0.22, 95% CI: 0.11–0.47). HIPEC was not associated with increased complications. The occurrence of postoperative renal dysfunction was significantly higher in the HIPEC group (OR 3.94, 95% CI: 1.85–8.38). Conclusion: The role of HIPEC in AGC has evolved over the past decade. HIPEC may improve survival rates and reduce recurrence rates in patients with AGC, without significant increase in complications and with a favorable impact on 3 and 5-year survival.
Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy
Authors: Shivakumar K Reddy, Abhijna R Ballal, S Shailaja, Raviraja N Seetharam, Chandrashekar H Raghu, Runali Sankhe, Kanthilatha Pai, Tenzin Tender, Mary Mathew, Annayya Aroor, Ashok K Shetty, Shalini Adiga, Vasudha Devi, Manjunatha S Muttigi, Dinesh Upadhya
Journal: Theranostics (2023)

Diabetic retinopathy (DR) is associated with retinal neovascularization, hard exudates, inflammation, oxidative stress and cell death, leading to vision loss.Anti-vascular endothelial growth factor (Anti-VEGF) therapy through repeated intravitreal injections is an established treatment for reducing VEGF levels in the retina for inhibiting neovascularization and leakage of hard exudates to prevent vision loss.Although anti-VEGF therapy has several clinical benefits, its monthly injection potentially causes devastating ocular complications, including trauma, intraocular hemorrhage, retinal detachment, endophthalmitis, etc. Methods: As mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) demonstrated safety in clinical studies, we have tested the efficacy of MSC-derived small EVs (MSC-sEVs) loaded anti-VEGF drug bevacizumab in a rat model of DR. Results:The study identified a clinically significant finding that sEV loaded with bevacizumab reduces the frequency of intravitreal injection required for treating diabetic retinopathy.The sustained effect is observed from the reduced levels of VEGF, exudates and leukostasis for more than two months following intravitreal injection of sEV loaded with bevacizumab, while bevacizumab alone could maintain reduced levels for about one month.Furthermore, retinal cell death was consistently lower in this period than only bevacizumab. Conclusion:This study provided significant evidence for the prolonged benefits of sEVs as a drug delivery system.Also, EV-mediated drug delivery systems could be considered for clinical application of retinal diseases as they maintain vitreous clarity in the light path due to their composition being similar to cells.
Assessment of Use of <i>ICD-9</i> and <i>ICD-10</i> Codes for Social Determinants of Health in the US, 2011-2021
Authors: Amil R. Agarwal, Laura Prichett, Amit Jain, Uma Srikumaran
Journal: JAMA Network Open (2023)

This cross-sectional study examines trends in the use of International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes for social determinants of health in the US from 2011 to 2021.
Letter regarding “Is liver biopsy essential to identifying the immune tolerant phase of chronic hepatitis B?”
Authors: Halil Haldun Emiroglu
Journal: Clinical and Molecular Hepatology (2023)

Dear Editor, I read with great interest the editorial paper by Oh and Sinn [1] entitled “Is liver biopsy mandatory to identify immunetolerant phase of chronic hepatitis B?” published online ahead of print. In their paper, Oh and Sinn [1] suggested that the status of patients presumed to be in the immune-tolerant phase without histological information should be carefully evaluated. I would like to draw attention to the following printing error related to the normal serum alanine aminotransferase (ALT) levels according to the American Association for the Study of Liver Disease (AASLD) guidelines. The recommended normal serum ALT level for males was incorrectly written as “&lt;33 U/L” in both the text and Table 1. However, according to the AASLD 2018 hepatitis B guidance [2], the upper limit of normal for ALT in males is 35 U/L. I believe that correcting this printing error will prevent any possible confusion in daily practice guiding management decisions.